Pre-metered dose magazine for dry powder inhaler

ABSTRACT

A dry powder inhaler including a housing having a mouthpiece and a delivery passageway connected to the mouthpiece, a magazine positioned within the housing and including a plurality of reservoirs for holding doses of dry powder, and wherein the magazine is movable within the housing so that the reservoirs are sequentially positioned within the delivery passageway of the housing upon movement of the magazine, a cover connected to the housing and movable to open and close the mouthpiece of the housing, and a rake connected to the cover, extending into the housing and engageable with the magazine so that, upon the cover being moved to open the mouthpiece, the rake moves the magazine and causes one of the reservoirs of the magazine to be positioned within the delivery passageway.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.10/783,796, filed Feb. 20, 2004, the disclosure of which is herebyincorporated by reference herein, and claims priority of United KingdomPatent Application No. 0303870.0, filed on Feb. 20, 2003.

FIELD OF THE INVENTION

The present disclosure relates to a dry powder inhaler for administeringdry powder medicament to a patient. More particularly, the presentdisclosure relates to a magazine having a plurality of individuallyseparated, pre-metered doses for a breath-actuated dry powder inhalerand a method for providing pre-metered doses of dry powder medicamentfor inhalation by a patient.

BACKGROUND OF THE INVENTION

Metered dose medicament inhalers are well known for dispensingmedicament to the lungs of a patient. In most cases, the inhalersinclude a reservoir containing dry powder medicament in bulk form, andmeans for metering the medicament from the reservoir in discrete amountsfor inhalation by a patient.

For example, U.S. Pat. No. 5,503,144, which is assigned to the assigneeof the present disclosure shows a breath-actuated dry-powder inhalerhaving a medicament reservoir. The reservoir contains dry powdermedicament in bulk form, and the inhaler includes a metering chamber forremoval of the powdered medicament from the reservoir in discreteamounts. The inhaler also includes an air inlet for entraining theremoved powdered medicament through a mouthpiece upon patientinhalation. The reservoir and metering chamber of the inhaler shown byU.S. Pat. No. 5,503,144 properly function to dispense discrete amountsof powdered medicament to a patient.

U.S. Pat. No. 6,655,381, which is assigned to the assignee of thepresent disclosure shows a pre-metered dose assembly for consistentlysupplying precise doses of medicament for a dry powder inhaler. Theassembly includes a cap defining a dry powder delivery passageway and amagazine including a plurality of separate reservoirs for holdingpre-metered doses of dry powder. The cap is movable with respect to themagazine for sequentially positioning the reservoirs within the deliverypassageway of the cap. A breath-induced low pressure through the drypowder delivery passageway of the assembly entrains dry powder from thereservoir positioned in the passageway for inhalation by a patient usingthe inhaler. Providing the powdered medicament in pre-metered dosesfurther ensures that the medicament is consistently dispensed to apatient in precise doses.

What is still desired is a new and improved dry powder inhaler foradministering dry powder medicament to a patient. The dry powder inhalerwill also preferably include a magazine having a plurality ofindividually separated and sealed, pre-metered doses and mechanisms foradvancing the magazine during use and for deploying the doses from themagazine for inhalation by a patient using the inhaler.

BRIEF SUMMARY OF THE INVENTION

The present disclosure provides a dry powder inhaler including a housinghaving a mouthpiece and a delivery passageway connected to themouthpiece, a magazine positioned within the housing and including aplurality of reservoirs for holding doses of dry powder, and wherein themagazine is movable within the housing so that the reservoirs aresequentially positioned within the delivery passageway of the housingupon movement of the magazine, a cover connected to the housing andmovable to open and close the mouthpiece of the housing, and a rakeconnected to the cover, extending into the housing and engageable withthe magazine so that, upon the cover being moved to open the mouthpiece,the rake moves the magazine and causes one of the reservoirs of themagazine to be positioned within the delivery passageway.

Further features and advantages of the presently disclosed pre-metereddose magazine and method for providing pre-metered doses will becomemore readily apparent to those having ordinary skill in the art to whichthe present disclosure relates from the following detailed descriptionand attached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

So that those having ordinary skill in the art will more readilyunderstand how to construct a pre-metered dose magazine and dry powderinhaler in accordance with the present disclosure, exemplary embodimentsare described in detail below with reference to the drawing figureswherein:

FIG. 1 is a side and top isometric view of an exemplary embodiment of adry powder inhaler according to the present disclosure including ahousing having a mouthpiece cover shown in a closed position;

FIG. 2 is a front and top isometric view of the inhaler of FIG. 1, withthe mouthpiece cover shown in an opened position to expose a mouthpieceof the inhaler;

FIG. 3 is a bottom plan view of an upper portion of the housing of theinhaler of FIG. 1;

FIG. 4 is a top plan view of a lower portion of the housing of theinhaler of FIG. 1;

FIG. 5 is a top plan view of a dose magazine of the inhaler of FIG. 1;

FIG. 6 is a side elevation view of the dose magazine of the inhaler ofFIG. 1;

FIG. 7 is a top plan view of a cup-like base of a de-agglomerator of theinhaler of FIG. 1;

FIG. 8 is a bottom isometric view of a top piece of the de-agglomeratorof the inhaler of FIG. 1;

FIG. 9 is a side elevation view of the cup-like base of thede-agglomerator of the inhaler of FIG. 1;

FIG. 10 is a top plan view of the mouthpiece cover of the inhaler ofFIG. 1, showing a magazine advancement rake pivotally extending from thecover;

FIG. 11 is a side elevation view of the mouthpiece cover and advancementrake of the inhaler of FIG. 1;

FIG. 12 is a top plan view of an exemplary embodiment of a dose magazineconstructed in accordance with the present disclosure;

FIG. 13 is a sectional view of the dose magazine taken along line 13-13of FIG. 12;

FIG. 14 is a top plan view of the dose magazine of FIG. 12, shown withan upper foil layer removed;

FIG. 15 is a top plan view of another exemplary embodiment of a dosemagazine constructed in accordance with the present disclosure;

FIG. 16 is a sectional view of the dose magazine taken along line 16-16of FIG. 15;

FIG. 17 is a top plan view of an additional exemplary embodiment of adose magazine constructed in accordance with the present disclosure;

FIG. 18 is a sectional view of the dose magazine taken along line 18-18of FIG. 17;

FIG. 19 is a top perspective view of a portion of a further exemplaryembodiment of a dose magazine constructed in accordance with the presentdisclosure, and including a foil removal mechanism;

FIG. 20 is a top plan view of a further exemplary embodiment of a dosemagazine constructed in accordance with the present disclosure;

FIG. 21 is a sectional view of the dose magazine taken along line 21-21of FIG. 20, showing a deployable medicament piston of the dose magazine;

FIG. 22 is a sectional view of exemplary embodiments of a dose magazine,a medicament piston, and an actuator, which is shown deploying thepiston, all constructed in accordance with the present disclosure;

FIG. 23 is a perspective view of the actuator of FIG. 22;

FIG. 24 is a side perspective view of additional exemplary embodimentsof a dose magazine, a mouthpiece cover and an actuator, all constructedin accordance with the present disclosure, and wherein the actuator isadapted to cause a medicament piston to be deployed from the magazineupon the mouthpiece cover being opened;

FIG. 25 is a front perspective view of the dose magazine, the mouthpiececover and the actuator of FIG. 24;

FIG. 26 is a sectional view of a further exemplary embodiment of a dosemagazine, a medicament piston, and an actuator shown deploying thepiston, all constructed in accordance with the present disclosure;

FIGS. 27 through 30 are side views of various exemplary embodiments ofmedicament pistons constructed in accordance with the presentdisclosure;

FIG. 31 is a side elevation view of another exemplary embodiment of amedicament piston constructed in accordance with the present disclosure;

FIG. 32 is a top plan view of the medicament piston of FIG. 31;

FIG. 33 is a side elevation view of an additional exemplary embodimentof a medicament piston constructed in accordance with the presentdisclosure;

FIG. 34 is a top plan view of the medicament piston of FIG. 33;

FIG. 35 is a side elevation view of another exemplary embodiment of amedicament piston constructed in accordance with the present disclosure;

FIG. 36 is a top plan view of the medicament piston of FIG. 35;

FIG. 37 is a side elevation view of an additional exemplary embodimentof a medicament piston constructed in accordance with the presentdisclosure;

FIG. 38 is a top plan view of the medicament piston of FIG. 37;

FIG. 39 is a top perspective view of a further exemplary embodiment of adose magazine constructed in accordance with the present disclosure;

FIG. 40 is a side elevation view of exemplary embodiments of a dosemagazine, an actuator for causing deployment of a medicament piston fromthe magazine, and an adjustment mechanism for adjusting the magnitude ofdeployment produced by the actuator, all constructed in accordance withthe present disclosure;

FIG. 41 is a top plan view of a further exemplary embodiment of a dosemagazine constructed in accordance with the present disclosure andincluding sets of deployable medicament pistons;

FIG. 42 is a side perspective view of a portion of the dose magazine ofFIG. 41, wherein a set of the medicament pistons is shown deployed, orextended upwardly, from a top surface of the magazine;

FIG. 43 is a side elevation view of a portion of the dose magazine ofFIG. 41, showing a set of actuators for causing deployment of a set ofthe medicament pistons from the magazine, and wherein the actuators canbe manipulated as desired to cause one or more of the pistons to bedeployed;

FIG. 44 is an end elevation view of a portion of the dose magazine ofFIG. 41, showing the set of actuators, wherein two out of four of theactuators have been manipulated to cause deployment of pistons;

FIG. 45 is a top and side perspective view of a further exemplaryembodiment of a dose magazine constructed in accordance with the presentdisclosure and including bores for receiving deployable medicamentpistons, and wherein the bores extend radially with respect to an axisof the magazine;

FIG. 46 is a sectional view of one of the bores of the dose magazine ofFIG. 45;

FIG. 47 is a top and side perspective view of another exemplaryembodiment of a dose magazine constructed in accordance with the presentdisclosure and including bores for receiving deployable medicamentpistons, wherein the bores extend radially and upwardly at an angle withrespect to an axis of the magazine;

FIG. 48 is a sectional view of one of the bores of the dose magazine ofFIG. 47;

FIG. 49 is a top plan view of an additional exemplary embodiment of adose magazine constructed in accordance with the present disclosure andincluding bores for receiving deployable medicament pistons, wherein thebores extend tangentially with respect to the magazine;

FIG. 50 is a top and side perspective view of another exemplaryembodiment of a dose magazine constructed in accordance with the presentdisclosure and including bores for receiving deployable medicamentpistons, wherein the bores are positioned at an outer circumference ofthe magazine and extend axially with respect to an axis of the magazine;

FIG. 51 is a top plan view of a further exemplary embodiment of arotatable dose magazine constructed in accordance with the presentdisclosure and including radially extending teeth for engaging a pawl,as shown, to prevent reverse rotation of the magazine and to provide anindication of the advancement of a final dose of the magazine;

FIGS. 52 and 53 are side elevation views of an exemplary embodiment of apawl constructed in accordance with the present disclosure, for engaginga dose magazine;

FIG. 54 is a top plan view of another exemplary embodiment of arotatable dose magazine constructed in accordance with the presentdisclosure and including radially extending medicament dose containers,and wherein a fixed blade is positioned for successively opening thedose containers upon rotation of the magazine;

FIG. 55 is a side elevation view of an exemplary embodiment of a strawconstructed in accordance with the present disclosure and includingmedicament dose containers, and wherein an exemplary embodiment of ablade constructed in accordance with the present disclosure forsuccessively opening the dose containers upon linear movement of thestraw is shown;

FIG. 56 is a side elevation view of another exemplary embodiment of astraw constructed in accordance with the present disclosure andincluding medicament dose containers, and wherein parallel layers of thestraw are pealed apart and wound to cause linear movement of the strawand successively open the dose containers;

FIG. 57 is a side elevation view of an exemplary embodiment of amedicament dose carrier constructed in accordance with the presentdisclosure and having doses of medicament attached to a surface of thecarrier, and wherein the carrier is shown being worked around a sharpcorner to release doses of the medicament from the carrier as thecarrier is bent around the corner; and

FIG. 58 is a side elevation view of a further exemplary embodiment of astraw constructed in accordance with the present disclosure andincluding medicament dose containers, and wherein the straw is shownbeing worked around a sharp corner to successively open the dosecontainers as the containers are bent around the corner.

DETAILED DESCRIPTION

FIGS. 1 and 2 show an exemplary embodiment of a dry powder inhaler 10constructed in accordance with the present disclosure. The dry powderinhaler 10 includes a pre-metered dose magazine 12 (not viewable inFIGS. 1 and 2 but shown in FIGS. 5 and 6) that consistently furnishesprecise doses of dry powder, e.g., a dry powder medicament or medicamentcomposition, for inhalation by a patient using the dry powder inhaler10.

During use, the patient opens a mouthpiece cover 14 of the inhaler 10,inhales, then closes the cover. The mouthpiece cover 14 is also shown inFIGS. 10 and 11. The action of opening the cover 14 advances thepre-metered dose magazine 12, shown in FIGS. 5 and 6, presenting a dosefor inhalation. If the cover 14 is closed without taking the dose, thatdose is contained within the inhaler 10, and is not presented again forinhalation. Thus, there is no possibility for unintentional doubledosing. Partial opening of the cover 14 will allow the user to see anindication of the number of doses remaining without advancing themagazine. Due to the individually sealed doses within the inhaler 10, alevel of moisture protection is present with this inhaler.

As shown in FIGS. 1 and 2, the inhaler 10 includes a housing 18 havingan upper portion 20 mated to a lower portion 22. FIG. 3 is a bottom planview of the upper portion 20 of the housing 18, and FIG. 4 is a top planview of the lower portion 22 of the housing. FIGS. 5 and 6 show the dosemagazine 12 of the inhaler of FIGS. 1 and 2, and FIGS. 7 and 9 show acup-like base 24 of a de-agglomerator of the inhaler 10 of FIGS. 1 and 2and FIG. 8 shows a top piece 26 of the de-agglomerator. The cup-likebase 24 is received in the lower portion 22 of the housing 18 and thedose magazine 12 is received for rotation over the top piece 26 of thede-agglomerator and guided by the upper portion 20 of the housing 18.

During operation, the magazine 12 is movable with respect to the upperportion 20 of the housing 18 for sequentially positioning reservoirs 30of the magazine 12 within a delivery passageway 32 of the upper portion.Then, a breath-induced low pressure at an outlet port 34 (shown in FIGS.7 and 9) of the de-agglomerator causes an air flow, through the drypowder delivery passageway 32 into a dry powder supply port 36 (shown inFIG. 8) of the de-agglomerator. As shown best in FIG. 3, the passageway32 of the upper portion 20 includes a venturi (or venturi-typerestriction) that causes the velocity of the breath-induced air flow toincrease. The air pressure in the venturi decreases as a result of theincreased velocity, and the drop in pressure causes the pre-metered doseof dry powder to be dragged from the reservoir 30 aligned with thepassageway 32, and entrained into the air flow traveling to thede-agglomerator.

Preferably, the magazine 12 is movable with respect to the upper portion20 of the housing for sequentially positioning the dry powder reservoirs30 of the magazine within the delivery passageway 32 of the upperportion. However, it should be understood that the magazine 12 could bemade stationary, and the upper portion 20 made movable with respect tothe magazine for sequentially positioning the passageway over thereservoirs.

The magazine 12 is provided with an annular shape such that rotation ofthe annular magazine sequentially positions the plurality of the drypowder reservoirs 30 within the delivery passageway 32 of the upperportion 20 of the housing 18. The annular magazine 12 includes teeth 40extending radially outwardly that are engaged by a pivotal rake 42 ofthe mouthpiece cover 14 for advancing the magazine 12 upon the cover 14being opened. FIGS. 10 and 11 show the magazine advancement rake 42pivotally extending from the cover 14. The engagement rake 42 engagesthe teeth 40 of the magazine 12 to rotate and advance the magazine 12upon the mouthpiece cover 14 being opened.

The dry powder reservoirs 30 are provided in the top surface of themagazine 12 and are uniformly sized and spaced with respect to oneanother. The magazine 12 preferably includes a seal over the top surfacefor sealing the doses of dry powder in the reservoirs 30 of the magazinein a moisture resistant and airtight manner prior to the reservoirsbeing positioned within the delivery passageway 32 of the upper portion20. The seal can comprise, for example, a metal foil secured to theannular top surface of the magazine 12 with adhesive and covering thedry powder in the reservoirs 30 in a moisture resistant and airtightmanner. The upper portion 20 of the housing 18 can include means forpiercing the foil above each of the reservoirs 30 prior to thereservoirs being positioned within the delivery passageway 32 of theupper portion. The means for piercing can comprise, for example, a bladeextending downward from the upper portion 20 of the housing 18 in frontof the venturi of the delivery passageway 32.

It is intended that a manufacturer will fill the reservoirs 30 of themagazine 12 with properly metered individual doses of dry powdermedicament, or a medicament composition including medicament and asuitable particulate carrier such as lactose. The filled reservoirs 30are then sealed in a moisture resistant and airtight manner, with thefoil for example, and the magazine 12 and the upper portion 20 of thehousing 18 are provided assembled as part of the inhaler 10. The inhaler10 and the magazine 12 may be disposable. Alternatively, the dosemagazine 12 may be removably insertable into a non-disposable inhaler 10so that an empty magazine can be replaced by a full magazine.

Preferably, the magazine 12 is movable with respect to the upper portion20 of the housing 18 through a plurality of discrete increments, whereinat each increment one of the plurality of the dry powder reservoirs 30of the magazine is positioned within the delivery passageway 32 of theupper portion. In addition, the magazine 12 is preferably movable in asingle direction only with respect to the housing 18, so that a user canaccess the reservoirs 30 in sequence, without being able to access oneof the reservoirs 30 more than once. Furthermore, movement between themagazine 12 and the upper portion 20 of the housing is preferablyprevented after all the dry powder reservoirs 30 of the magazine havebeen positioned in the delivery passageway 32 of the upper portion, toprovide an indication to a patient that all of the doses of the magazinehave been used. For example, the magazine 12 is provided with a radiallyinwardly extending catch 44, as shown in FIG. 5, that prevents furtherrotation of the magazine upon all of the reservoirs 30 passing throughthe delivery passageway 32 of the housing 18.

The inhaler 10 can also include an indicator for indicating the numberof dry powder reservoirs 30 containing dry powder, i.e., the number ofpre-metered doses remaining in the magazine 12. The indicator cancomprise, for example, sequential printed numbers corresponding to thereservoirs 30 of the magazine 12 provided on the outer surface of themagazine, so that the number of reservoirs that have passed through thedelivery passageway 32 of the upper portion 20 of the housing 18 can bedetermined by partly opening the cover 14 (without causing the magazineto advance) and viewing the numbers on the magazine. Although not shown,the inhaler can also be provided with a lock for locking the mouthpiececover 14 in an opened or closed position upon the advancement of a finalmedicament reservoir of the magazine.

As its name implies, the de-agglomerator breaks down agglomerates of drypowder before inhalation of the dry powder by a patient. Thede-agglomerator includes two diametrically opposed inlet ports 46 thatextend in a direction substantially tangential to the circularcross-section of the swirl chamber formed within the de-agglomerator. Asa result, air flows entering the chamber through the inlet ports 46 areat least initially directed transverse with respect to the chamber andcollide with the air flow entering through the supply port to create acombined turbulent air flow.

The de-agglomerator includes vanes 48 at the first end of the swirlchamber 52. The vanes 48 are sized such that at least a portion of thecombined air flows collide with oblique surfaces of the vanes. Thegeometry of the swirl chamber 52 causes the combined air flows and theentrained dry powder to follow a turbulent spiral path, or vortex,through the chamber. Thus, particles and any agglomerates of the drypowder constantly impact against the wall of the swirl chamber andcollide with each other, resulting in a mutual grinding or shatteringaction between the particles and agglomerates. In addition, particlesand agglomerates deflected off the oblique surfaces of the vanes 48cause further impacts and collisions. The constant impacts andcollisions cause any agglomerates of dry powder to break into additionalparticles, and cause the particles to be substantially micronized.

Upon exiting the swirl chamber 52, the direction of the combined airflow and the entrained dry powder is again changed through the outletport 34, which extends through the mouthpiece 16 of the housing 18. Thecombined air flow and the entrained dry powder retain a swirl componentof the flow, such that the air flow and the entrained dry powderspirally swirl through the outlet port 34. Since the micronized powderand any remaining agglomerates maintain the swirl imparted from theswirl chamber, the swirling flow causes additional impacts in the outletport 34 so as to result in further breaking up of any remainingagglomerates prior to being inhaled by a patient. The de-agglomerator,therefore, ensures that particles of the dry powder are small enough foradequate penetration of the powder into a bronchial region of apatient's lungs during inhalation.

The de-agglomerator is assembled from two pieces: the cup-like base 24shown in FIGS. 7 and 9, and the top piece 26 shown in FIG. 8, which areconnected together to form the swirl chamber 52 within thede-agglomerator. The cup-like base 24 is secured in the lower portion 22of the housing 18 and defines the outlet port 34 and the inlet ports 46.The top piece 26 forms the vanes 48 and defines the supply port 36.

The top piece 26 also includes an upwardly extending cylindrical guide50, and a chimney (not viewable) extending upwardly from the supply port36 within the guide, as shown best in FIG. 8. The inner circumference ofthe annular magazine 12 is received coaxially on the guide 50, such thatthe magazine can be rotated about the guide. A hood of the upper portion20 of the housing 18 is received over the chimney of the supply port 36to connect the delivery passageway 32 of the upper portion 30 with thesupply port 36 of the de-agglomerator.

The de-agglomerator, the magazine and the housing are preferablymanufactured from a plastic such as polypropylene, acetal or mouldedpolystyrene, but may be manufactured from metal or another suitablematerial.

The inhaler of FIGS. 1 through 11 may be used for any drug formulationwhich may be advantageously administered to the lung or nasal passagesin an animal, to cure or alleviate any illness or its symptoms. Manymedicaments, bioactive active substances and pharmaceutical compositionsmay be included in the dosage forms of the present invention.Non-limiting examples of classes of drugs contemplated for use includeace-inhibitors, acne drugs, alkaloids, amino acid preparations, anabolicpreparations, analgesics, anesthetics, antacids, antianginal drugs,anti-anxiety agents, anti-arrhythmias, anti-asthmatics, antibiotics,anti-cholesterolemics, anti-coagulants, anti-convulsants,anti-depressants, anti-diabetic agents, anti-diarrhea preparations,antidotes, anti-emetics, anti-histamines, anti-hypertensive drugs,anti-inflammatory agents, anti-lipid agents, anti-manics,anti-nauseants, anti-neoplastics, anti-obesity drugs, anti-parkinsonismagents, anti-psychotics, anti-pyretics, anti-rheumatic agents,anti-spasmodics, anti-stroke agents, anti-thrombotic drugs, anti-thyroidpreparations, anti-tumor drugs, anti-tussives, anti-ulcer agents,anti-uricemic drugs, anti-viral drugs, appetite stimulants orsuppressants, biological response modifiers, blood modifiers, bonemetabolism regulators, cardiovascular agents, central nervous systemstimulates, cerebral dilators, cholinesterase inhibitors,contraceptives, coronary dilators, cough suppressants, decongestants,dietary supplements, diuretics, DNA and genetic modifying drugs,dopamine receptor agonists, endometriosis management agents, enzymes,erectile dysfunction therapies, erythropoietic drugs, expectorants,fertility agents, gastrointestinal agents, homeopathic remedies,hormones, hyper- and hypo-glycemic agents, hypercalcemia andhypocalcemia management agents, hypnotics, immunomodulators,immunosuppressives, ion exchange resins, laxatives, migrainepreparations, motion sickness treatments, mucolytics, muscle relaxants,neuromuscular drugs, obesity management agents, osteoporosispreparations, oxytocics, parasympatholytics, parasympathomimetics,peripheral vasodilators, prostaglandins, psychotherapeutic agents,psycho-tropics, stimulants, respiratory agents, sedatives, smokingcessation aids, sympatholytics, systemic and non-systemic anti-infectiveagents, terine relaxants, thyroid and anti-thyroid preparations,tranquilizers, tremor preparations, urinary tract agents,vasoconstrictors, vasodilators, and combinations thereof.

In some embodiments of the invention, the dosage form for use with theinvention comprises anti-inflammatory agents suitable for inhalationadministration. Such anti-inflammatory agents may include, for example,bronchodilators and steroids. Representative β₂-adrenergic receptoragonist bronchodilators include, without limitation, salmeterol,formoterol, bambuterol, albuterol, terbutaline, pirbuterol, bitolterol,metaproterenol, isoetharine, isoproterenol, fenoterol, or procaterol.Non-limitating anti-inflammatory steroids contemplated for use with theinvention include budesonide, beclomethasone, fluticasone, andtriamcinolone diacetate. Additional anti-inflammatory agentscontemplated include ipatropium bromide and sodium cromoglycate.

Therapeutically effective formulations and dosages to be administeredusing the devices described herein are well known to practitioners. Oneof skill in the art will appreciate that practitioners may opt to alterdosages and/or formulations to fit a particular patient/animal need.

FIGS. 12 through 14 show an exemplary embodiment of a dose magazine 60constructed in accordance with the present disclosure. The dose magazine60 can be used, for example, with the inhaler of FIGS. 1 through 11. Asshown in FIG. 14, the dose magazine 60 includes medicament reservoirs inthe form of axial bores 62 for receiving medicament. As shown in FIGS.12 and 13, the dose magazine 60 also includes a lower layer 64 ofmoisture resistant, air-tight material covering a lower surface of themagazine and an upper layer 66 of moisture resistant, air-tight materialcovering an upper surface of the magazine and enclosing medicament inthe bores 62 of the magazine in a dry, air-tight manner. As shown bestin FIG. 13, the upper layer 66 of moisture resistant, air-tight materialcan be provided with domes 68 over the medicament bores 62 so that ablade 70 can be positioned to successively cut open the domes 68 andrelease the medicament upon rotation of the magazine 60.

The moisture resistant, air-tight material can comprise, for example,metal foil secured to the magazine with adhesive. In addition, the foillayers may include selective adhesive, e.g., no adhesive positioned incontact with the medicament, in order to maintain dose uniformity. Themoisture resistant, air-tight material can also comprise, for example, alaminate of metal foil secured to a layer of plastic, which in turn issecured to the magazine with adhesive.

FIGS. 15 and 16 show another exemplary embodiment of a dose magazine 80constructed in accordance with the present disclosure. As shown, themagazine 80 includes medicament reservoirs 82 and each medicamentreservoir includes a lining 84 of moisture resistant, air-tightmaterial, such as a metal insert or foil.

FIGS. 17 and 18 show an additional exemplary embodiment of a dosemagazine 90 constructed in accordance with the present disclosure. Asshown, the magazine 90 includes medicament reservoirs 92 formed in atrough 94 of a first material, such as plastic, which is formed in atrough 96 of moisture resistant, air-tight material, such as a metal.The metal trough 96 can be pre-formed via stamping or metal injectionmolding. The metal trough 96 can also be formed from a metal foil.

FIG. 19 shows a further exemplary embodiment of a dose magazine 100constructed in accordance with the present disclosure, and including afoil removal mechanism 102. The foil removal mechanism comprises arotatable winding wheel 102 which peels an upper layer 104 of moistureresistant, air-tight material, such as metal foil, from an upper surfaceof the magazine 100 as the magazine is rotated. As the foil 104 ispeeled from the magazine 100, medicament reservoirs 106 are uncovered toallow inhalation of the medicament therein. The foil removal mechanism102 can also be adapted and used to index the magazine 100.

FIGS. 20 and 21 show a further exemplary embodiment of a dose magazine110 constructed in accordance with the present disclosure. The dosemagazine 110 includes axial bores 112 containing deployable medicamentpistons 114 sealed between layers 116, 118 of moisture resistant,air-tight material, such as metal foil. The pistons 114 each have atleast one compartment 120 holding at least one dose of powdermedicament, which are presented for inhalation upon the pistons 114being pushed upwardly through the upper layer 116 of foil.

FIG. 22 shows exemplary embodiments of a dose magazine 130, a medicamentpiston 132, and an actuator 134, which is shown deploying the piston,all constructed in accordance with the present disclosure. FIG. 23 is aperspective view of the actuator 134 of FIG. 22. As the magazine 130 islinearly moved over the actuator 134, the actuator 134 successivelypushes the pistons 132 upwardly through the upper layer 116 of foil toexpose a compartment 136 containing a dose of medicament for inhalation.

FIGS. 24 and 25 show additional exemplary embodiments of a dose magazine140, a mouthpiece cover 142 and an actuator 144, all constructed inaccordance with the present disclosure, and wherein the actuator 144 isadapted to cause a medicament piston 146 to be deployed from themagazine 140 upon the mouthpiece cover 142 being opened.

FIG. 26 shows a further exemplary embodiment of a dose magazine 150, amedicament piston 152, and an actuator 154 shown deploying the piston,all constructed in accordance with the present disclosure. Themedicament piston 152 includes multiple, vertically arrangedcompartments in the form of shoulders 156 a, 156 b, 156 c for holdingdry powder medicament. By varying the amount that the piston 152 isextended through the upper layer 116 of foil, the amount of medicamentfor inhalation can be varied. For example, the piston 152 can beextended through the foil 116 so that only one shoulder 156 a out of thethree shoulders 156 a, 156 b, 156 c of the piston extends above the foilso that a minimum dose is exposed for inhalation. Alternatively, thepiston 152 can be extended through the foil 116 so that all of theshoulders 156 a, 156 b, 156 c of the piston extend above the foil sothat a maximum dose is exposed for inhalation.

FIGS. 27 through 30 show various exemplary embodiments of medicamentpistons 160, 162, 164, 166 constructed in accordance with the presentdisclosure. The piston 160 of FIG. 27 includes vertically arrangedshoulders 168 a, 168 b, 168 c for supporting dry powder medicament, andthe shoulders 168 a, 168 b, 168 c become smaller towards the bottom ofthe piston 160. The piston 162 of FIG. 28 includes vertically arrangedcompartments 170 a, 170 b, 170 c for holding dry powder medicament, andthe compartments 170 a, 170 b, 170 c become larger towards the bottom ofthe piston. The piston 164 of FIG. 29 includes vertically arrangedshoulders 172 for holding dry powder medicament, and the shoulders areequally sized. The piston 166 of FIG. 30 includes vertically arrangedcompartments 174 for holding dry powder medicament, and the compartmentsare equally sized.

FIGS. 31 through 38 show further exemplary embodiments of medicamentpistons 180, 182, 184, 186 constructed in accordance with the presentdisclosure. The piston 180 of FIGS. 31 and 32 has a circularcross-section and includes a single compartment 190 for holding drypowder medicament. The piston 182 of FIGS. 33 and 34 has a circularcross-section and includes vertically arranged shoulders 192 for holdingdry powder medicament, and the shoulders 192 are equally sized. Thepiston 184 of FIGS. 35 and 36 has a rectangular cross-section andincludes a single compartment 194 for holding dry powder medicament. Thepiston 186 of FIGS. 37 and 38 has a rectangular cross-section andincludes vertically arranged compartments 196 for holding dry powdermedicament, and the compartments 196 are equally sized.

FIG. 39 is a top perspective view of a further exemplary embodiment of adose magazine 200 constructed in accordance with the present disclosure.The dose magazine 200 includes examples of variously shaped and arrangedbores for receiving deployable medicament pistons, such as themedicament pistons of FIGS. 27 through 38, for example. The magazine 200can include, for example, circular bores 202 that extend radiallythrough the magazine or circular bores 204 that extend axially throughthe magazine. The magazine 200 can also include rectangular bores 206that extend radially through the magazine or rectangular bores 208 thatextend axially through the magazine. In addition, the magazine 200 caninclude a set 210 of radially arranged, rectangular bores or a set 212of radially extending, rectangular bores.

FIG. 40 shows exemplary embodiments of a dose magazine 220, an actuator222 for causing deployment of a medicament piston 224 from the magazine,and an adjustment mechanism 226 for adjusting the magnitude ofdeployment produced by the actuator, all constructed in accordance withthe present disclosure. The adjustment mechanism 226 can be adjusted bya user to adjust the magnitude of deployment of the piston 224 producedby the actuator 222, so that the amount of dry powder medicament exposedfor inhalation can be adjusted. The adjustment mechanism 226 includesshims 228 which prevent full motion of actuator 222, and a user can dialin the number of shims 228 corresponding to a desired dose.

FIG. 41 is a top plan view of a further exemplary embodiment of a dosemagazine 230 constructed in accordance with the present disclosure andincluding sets 232 of deployable medicament pistons, and FIG. 42 is aside perspective view of a portion of the dose magazine 230 of FIG. 41,wherein a set 232 of the medicament pistons 234 a, 234 b, 234 c, 234 dis shown deployed, or extended upwardly, from a top surface of themagazine. FIGS. 43 and 44 show a set 236 of actuators 238 a, 238 b, 238c, 238 d for causing deployment of the set 232 of the medicament pistons234 a, 234 b, 234 c, 234 d from the magazine. The actuators 238 a, 238b, 238 c, 238 d can be manipulated as desired by a user to cause one ormore of the pistons 234 a, 234 b, 234 c, 234 d to be deployed, so thatthe amount of dry powder medicament exposed for inhalation can beadjusted.

FIGS. 45 and 46 show a further exemplary embodiment of a dose magazine240 constructed in accordance with the present disclosure and includingbores 242 for receiving deployable medicament pistons. The bores 242extend radially with respect to an axis A of the magazine 240.

FIGS. 47 and 48 show another exemplary embodiment of a dose magazine 250constructed in accordance with the present disclosure and includingbores 252 for receiving deployable medicament pistons. The bores 252extend radially and at an angle with respect to an axis A of themagazine 250.

FIG. 49 shows an additional exemplary embodiment of a dose magazine 260constructed in accordance with the present disclosure and includingbores 262 for receiving deployable medicament pistons. The bores 262extend tangentially with respect to the magazine 260.

FIG. 50 shows a further exemplary embodiment of a dose magazine 270constructed in accordance with the present disclosure and includingbores 272 for receiving deployable medicament pistons. The bores 272 arepositioned at an outer circumference of the magazine 270 and extendaxially with respect to an axis A of the magazine.

FIG. 51 shows a further exemplary embodiment of a rotatable dosemagazine 280 constructed in accordance with the present disclosure andincluding radially extending teeth 282 for engaging a pawl 284, asshown, to prevent reverse rotation of the magazine 280 and to provide anindication of the advancement of a final medicament reservoir 286 of themagazine. This mechanism can be used to increase the force required toadvance the magazine 280, increase noise or vibration, or provide otherindication that the last medicament reservoir 286 is approaching and theinhaler should be refilled or replaced.

FIGS. 52 and 53 show an exemplary embodiment of a pawl 294 constructedin accordance with the present disclosure, for engaging a dose magazine290. The pawl 294 can be adapted to provide a different sounding noiseupon the advancement of a final medicament reservoir 296 and extendingtooth 292 of the magazine 290.

FIG. 54 shows another exemplary embodiment of a rotatable dose magazine300 constructed in accordance with the present disclosure and includingradially extending medicament dose containers 302 and a fixed blade 304for successively opening the dose containers upon rotation of themagazine.

FIG. 55 shows an exemplary embodiment of a dose magazine 310 constructedin accordance with the present disclosure and including medicament dosecontainers 312, and wherein an exemplary embodiment of a blade 314constructed in accordance with the present disclosure for successivelyopening the dose containers 312 upon linear movement of the magazine 310is shown.

FIG. 56 shows another exemplary embodiment of a dose magazine 320constructed in accordance with the present disclosure and includingmedicament dose containers 322, and wherein parallel layers 324, 326 ofthe dose magazine are peeled apart and wound to cause linear movement ofthe dose magazine 320 and successive opening of the dose containers 322contained between the layers 324, 326.

FIG. 57 shows an exemplary embodiment of a medicament dose magazine 330constructed in accordance with the present disclosure and having doses332 of medicament attached to a surface of the magazine 330. Themagazine 330 is made of elastic material and is drawn around a sharpcorner 334 to successively release the doses 332 of the medicament fromthe magazine 330 as the magazine is bent around the corner 334.

FIG. 58 shows a further exemplary embodiment of a dose magazine 340constructed in accordance with the present disclosure and includingmedicament dose containers 342. The dose magazine 340 is drawn around asharp corner 344 to successively open the dose containers 342 as thecontainers are bent around the corner.

It should be understood that the foregoing detailed description andexemplary embodiments are only illustrative of a dry powder medicamentinhaler and elements thereof according to the present disclosure.Various alternatives and modifications to the presently disclosedinhaler and inhaler elements can be devised by those skilled in the artwithout departing from the spirit and scope of the present disclosure.Accordingly, the present disclosure is intended to embrace all suchalternatives and modifications that fall within the spirit and scope ofthe present disclosure and the following claims.

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 37. A dry powder inhaler, comprising: a housing having a mouthpiece and a delivery passageway connected to the mouthpiece; a magazine positioned within the housing and including a plurality of reservoirs for holding doses of dry powder, the magazine being movable within the housing to sequentially position the reservoirs within the delivery passageway, the magazine including a layer of moisture resistant, air-tight material secured to an upper surface of the magazine over the reservoirs; a de-agglomerator positioned between the magazine and the mouthpiece for creating turbulent airflow; a cover connected to the housing and selectively movable to open and close access to the mouthpiece; a rake connected to the cover and extending into the housing, the rake being engageable with the magazine so that, upon movement of the cover to open access to the mouthpiece, the rake moves the magazine and causes one of the reservoirs to be positioned within the delivery passageway; and a foil removal mechanism having a rotatable winding wheel that peels the layer of moisture resistant, air-tight material from the upper surface of the magazine as the magazine is moved.
 38. A dry powder inhaler, comprising: a housing having a mouthpiece and a delivery passageway connected to the mouthpiece; a magazine positioned within the housing and including a plurality of reservoirs adapted to hold doses of dry powder, the magazine being movable within the housing to sequentially position the reservoirs within the delivery passageway; a cover connected to the housing and selectively movable to open and close access to the mouthpiece; and a rake connected to the cover and extending into the housing, the rake being engageable with the magazine so that, upon movement of the cover to open access to the mouthpiece, the rake moves the magazine and causes one of the reservoirs to be positioned within the delivery passageway; wherein the magazine includes a pair of continuous strips of material which define the plurality of reservoirs, the strips being separable from one another so as to open the reservoir positioned within the delivery passageway.
 39. An inhaler according to claim 38, wherein each strip is wound on a post following separation.
 40. An inhaler according to claim 38, further comprising a de-agglomerator positioned between the magazine and the mouthpiece for creating turbulent airflow.
 41. An inhaler according to claim 38, wherein the magazine is rotatably movable with respect to the housing in only a single direction.
 42. An inhaler according to claim 38, further comprising an indicator for indicating the number of reservoirs containing dry powder remaining in the magazine.
 43. An inhaler according to claim 38, further comprising dry powder medicament contained in the reservoirs of the magazine.
 44. An inhaler according to claim 38, wherein the strips are formed from a moisture resistant, air-tight material.
 45. An inhaler according to claim 38, further comprising means for determining when a last one of the reservoirs has been positioned within the delivery passageway.
 46. A dry powder inhaler, comprising: a housing having a mouthpiece and a delivery passageway connected to the mouthpiece; a strip of material positioned within the housing and defining a plurality of reservoirs adapted to hold doses of dry powder, the strip of material being movable within the housing to sequentially position the reservoirs within the delivery passageway; a cover connected to the housing and selectively movable to open and close access to the mouthpiece; and a rake connected to the cover and extending into the housing, the rake being engageable with the strip of material so that, upon movement of the cover to open access to the mouthpiece, the rake moves the strip of material and causes one of the reservoirs to be positioned within the delivery passageway; and means for opening the reservoir positioned within the delivery passageway to release a dose of dry powder.
 47. An inhaler according to claim 46, wherein the means for opening the reservoir separates a first portion of the strip of material from a second portion of the strip of material.
 48. An inhaler according to claim 47, further comprising a first post for winding the first portion of the strip of material and a second post for winding the second portion of the strip of material.
 49. An inhaler according to claim 46, further comprising a de-agglomerator positioned between the strip of material and the mouthpiece for creating turbulent airflow.
 50. An inhaler according to claim 46, wherein the strip of material is rotatably movable with respect to the housing in only a single direction.
 51. An inhaler according to claim 46, further comprising an indicator for indicating the number of reservoirs containing dry powder remaining in the strip of material.
 52. An inhaler according to claim 46, further comprising dry powder medicament contained in the reservoirs in the strip of material.
 53. An inhaler according to claim 46, wherein the strip of material is formed from a moisture resistant, air-tight material. 